The present invention relates to the synthesis of sophisticated compounds or compositions in relatively small amounts (e.g., grams rather than kilograms). The invention is particularly applicable for reactions carried out using complex manipulations (e.g., combinatorial chemistry) or to synthesize complex compositions such as peptides using solid phase peptide synthesis (SPPS).
A number of such processes have been successfully automated and in turn, automation has created a need to dispense and transfer small quantities of liquids accurately and precisely to (among other reasons) obtain a desired reaction, or to minimize the amounts of expensive materials used (avoid waste).
Additionally, depending upon the reaction scheme or desired product, the liquids may have different viscosities or other physical properties that make accurate dispensing of small volumes somewhat difficult. Because of such factors, an automated system should be able to handle a range of viscosities and other liquid properties in order to be most useful over a wide range of substances.
In some circumstances, the difficulty of dispensing small volumes relates to the relatively small openings, tubing or other passageways through which the liquid must pass. These can be susceptible to clogging and other problems.
In some cases, such as solid phase peptide synthesis, a number of reactions are carried out successively using different compositions (e.g., amino acids) that are added in a particular order. For the purpose of adding desired acids to a peptide chain, clogging or even simple residue of a previous acid will tend to cause an increase in the amount of undesired peptide relative to the desired peptide.
In a number of conventional instruments, small dispensed volumes are transferred using devices such as syringe pumps to displace a known volume of liquid into (for example) tubing which carries the liquid to its intended destination. Such techniques are based on the assumption that the volume displaced by the pump will accurately reach the intended location. In an expected manner, however, as required or desired volumes become smaller, relative error increases and in some cases can become significant.
In other applications, precise dispensing of small volumes is carried out using a variety of positive displacement fluid pumps which meter compositions to a desired destination. Nevertheless, such positive displacement pumps tend to be complex and expensive and require considerable maintenance.
Therefore, it remains a continuing goal to obtain accurate automated small volume dispensing systems that can handle liquids within a reasonable range of parameters and accurately dispense those liquids to desired locations.